Oxidative stress and free radicals have been implicated in the etiology of a number of diseases, including cancers, coronary heart diseases and type II diabetes. The human body has a number of endogenous free radicals scavenging systems which have genetic variability. The serum paraoxonase (PON) is an enzyme carried in the HDL that contributes to the detoxification of organophosphorus compounds but also of carcinogenic products of lipid peroxidation. Paraoxonase has been suggested to account for an important part of the antioxidative properties of HDL.sup.1-3. PON1 is polymorphic in human populations and different individuals also express widely different levels of this enzyme..sup.4-7
Two polymorphisms are currently known in human PON1. The Q191R polymorphism was the first mutation of PONI reported..sup.4,6 The second one is the missense mutation of A to T in codon 54, producing a substitution of methionine (M) to leucine (L) (Met45Leu.sup.4a ; known also as Met55Leu.sup.4). Both these polymorphisms have been shown to affect serum PON activity,.sup.6,8,9 and in particular, the L54 allele has been associated with an increased PON activity. There are a few previous studies concerned with the association of Met54Leu polymorphism and coronary heart disease (CHD), the findings are, however, inconclusive.sup.8. To our knowledge, only two studies concerning the association of the Met54Leu polymorphism with CHD have been published..sup.8,10 In a cross-sectional study, the prevalence of LL homozygosity was twofold among diabetics who already had clinical CHD compared with diabetics who had no clinical CHD, even though LL homozygotes had 1.7-fold PON activity, compared with MM homozygotes..sup.8 In a Japanese retrospective case-control study, Met54Leu PON polymorphism had no association with CHD..sup.10